乳腺癌组织中YTHDF1、USP28的表达及临床意义

Expression changes and clinical significance of YTHDF1 and USP28 in breast cancer tissues

目的探讨乳腺癌组织中YTH N6-甲基腺苷RNA结合蛋白1(YTHDF1)、泛素特异性蛋白酶28(USP28)的表达及意义。方法选取乳腺癌患者103例,应用实时荧光定量PCR法及免疫组化法检测癌组织和癌旁正常组织中YTHDF1、USP28 mRNA和蛋白表达。Spearman秩相关分析法分析YTHDF1、USP28蛋白表达的相关性。比较不同临床病理特征患者癌组织中YTHDF1、USP28蛋白阳性表达率差异。Kaplan-Meier生存分析(Log-Rank检验)法分析YTHDF1、USP28蛋白表达与患者临床预后的关系。单因素及多因素Cox回归分析影响乳腺癌患者临床预后的因素。结果乳腺癌组织中YTHDF1、USP28 mRNA及蛋白表达均高于癌旁正常组织(P均<0.05)。乳腺癌组织中YTHDF1蛋白表达与USP28蛋白表达呈正相关(r=0.613,P<0.05)。不同TNM分期、分化程度癌组织中YTHDF1、USP28蛋白阳性表达率比较差异均有统计学意义(P均<0.05)。YTHDF1阳性表达及阴性表达者3年总体生存率分别为77.14%(54/70)、90.91%(30/33),差异有统计学意义(P<0.05)。USP28阳性表达及阴性表达者3年总体生存率分别为76.71%(56/73)、90.91%(28/30),差异有统计学意义(P<0.05)。YTHDF1阳性表达、USP28阳性表达、TNM分期Ⅲ期、低分化程度是影响乳腺癌患者临床预后的独立危险因素(P均<0.05)。结论乳腺癌组织中YTHDF1、USP28表达升高,二者与TNM分期、分化程度有关,是影响乳腺癌患者临床预后的独立危险因素。

Objective To investigate the expression and significance of YTH N6-methyladenosine RNA binding pro⁃tein 1(YTHDF1)and ubiquitin specific protease 28(USP28)in the breast cancer tissues.Methods Totally 103 pa⁃tients with breast cancer were studied.Real-time fluorescent quantitative polymerase chain reaction(RT-qPCR)and immu⁃nohistochemistry were used to detect the expression levels of YTHDF1 and USP28 mRNA and protein in the cancer tissues and adjacent normal tissues.Spearman rank correlation analysis was used to analyze the correlation between YTHDF1 and USP28 protein expression.The differences in the positive rates of YTHDF1 and USP28 protein expression in the cancer tis⁃sues of patients with different clinical and pathological characteristics were compared.Kaplan-Meier survival analysis(Log-Rank test)was used to analyze the relationship between the expression of YTHDF1,USP28 proteins and clinical prognosis.Univariate and multivariate Cox regression analyses were used to analyze factors affecting the clinical prognosis of breast can⁃cer patients.Results The mRNA and protein expression levels of YTHDF1 and USP28 in the breast cancer tissues were significantly higher than those in the adjacent normal tissues,with statistically significant differences(all P<0.05).There was a significant positive correlation between YTHDF1 and USP28 protein expression in the breast cancer tissues(r=0.613,P<0.05).There were statistically significant differences in the positive rates of YTHDF1 and USP28 protein expres⁃sion between tumor tissues with different TNM stages and differentiation degrees(all P<0.05).The 3-year overall survival rates of patients with positive YTHDF1 expression and negative YTHDF1 expression were 77.14%(54/70)and 90.91%(30/33),respectively,with statistically significant difference(P<0.05).The 3-year overall survival rates of patients with positive USP28 expression and negative USP28 expression were 76.71%(56/73)and 90.91%(28/30),respectively,with statistically significant difference.YTHDF1 positive expression,USP28 positive expression,tumor stageⅢ,and poor differentiation were independent risk factors for survival and prognosis of breast cancer(all P<0.05).Conclusion The expression levels of YTHDF1 and USP28 increase in breast cancer tissues,and both of them are related to tumor TNM stage and differentiation,and are independent risk factors for poor survival and prognosis of breast cancer patients.